All rights reserved to text 2005.
TYPICAL ANIMAL CELL
http://training.seer.cancer.gov/module_anatomy/images/illu_cell_structure.jpg
Structures:
Golgi, Rough Endoplasmic Reticulum, Smooth Endoplasmic Reticulum,
Plasma
Membrane, Secreted Product (Secretion), Secretory Vesicle, Lysosome,
Small E.
R. Vesicle,
Nucleus, Chromatin (DNA + protein), Nucleolus, Nuclear Pore,
Mitochondrion,
Centriolar
Microtubules, and Ribosomes (free ).
CELLS - Chpater 2 of Marieb text, p. 64.
The cell theory was first put in writing by Oken in 1805, and later published by the botanist Schleiden and zoologist Schwann in 1839. It stated that all living things were composed of cells. The term cell (in this context) was coined by the early microscopist Robert Hooke who looked at cork and saw openings that looked like monastery cells or rectangular rooms.
The Functions of Cells
To understand how cells relate to their environment, we will examine the mathematical concept of the relationship between cell surface area and volume.
Cell Size: most cells are from 10 micrometers to 100 micrometers (0.1mm) in diameter. The smaller cell dimensions are limited by the size of first the macromolecules like the nucleic acids and proteins of bacteria, and of the internal organelles (tiny organs) of larger cells. The larger cell dimensions are determined by the cell surface/volume ratio. As cell size increases, the cell's ability to gather nutrients and get rid of wastes from its environment decreases as the cell surface, exposed to the environment, decreases relative to the cell's volume.
Computation of surface/volume ratios,
PROKARYOTIC CELLS VS EUKARYOTIC CELLS
The term prokaryotic means "before a nucleus." It includes the bacteria. These organisms have a cell membrane (most important organelle for defining a cell, polysaccharide cell wall, and ribosomes composed of the nucleic acid RNA and DNA. The DNA is not inside a membrane-enveloped nucleus. They do not have membrane-bound organelles.
Eukaryotic cells have a nucleus, an outer plasma membrane and membrane-bound organelles. In the following pages learn the organelle name, function and be able to recognize the appearance of each.
See cells in action at http://www.cellsalive.com/index.htm .
TRANSPORT ACROSS MEMBRANES
Cell Membrane - p. 68-71 of textbook.
Cell membrane is a fluid bilayer of phospholipids and globular proteins. Globular proteins that lie side by side and extend through the outer plasma membrane serve as facilitated transport channels for substances like glucose and amino acids. Other globular proteins will serve as active (energy expending) transport gated channels for ions like Sodium (Na+) and Potassium (K+). Many of the plasma membrane proteins have polysaccharides, glycolipids and protein chains projecting from its surface. Some serve as "cellular cement" for adhering to adjacent cells in a tissue layer. Other proteins allow for the recognition of cell type that is important for the immune system to recognize "self." A receptor may be an element of a transport channel. See below.
Many surface proteins serve as external membrane receptors for peptide hormones such as insulin, which causes the cell to increase its uptake of glucose from the extracellular fluid (ECF) by causing facilitated glucose (glut-4) transport channels to appear in the target cell's plasma membrane. The hormone insulin and its receptor have a lock and key relationship (insulin is the key), as do viruses and their receptor, and enzymes and substrates. There are G proteins in and adjacent to the membrane that act as second messengers (see chapter 18). Mutated genes can cause receptors to be absent, receptors may lose function, or the receptors may over-function. Disease results. Receptors also bind to neurotransmitters and lipoproteins.
Within the plasma membrane bilayer of phospholipids, cholesterol is embedded among the fatty acids tails of the cell membrane. It serves to stiffen the membrane by limiting the movement of the fatty acid tails of the phospholipids. Membrane not only covers the cell but also covers many of the internal organelles such as the nucleus, lysosomes and mitochondria. . Both the fatty acid tails and cholesterol, you remember, are nonpolar and hydrophobic, but they mix with each other. Water cannot stay in the interior if the membrane because it is polar. However, steroids hormones such as estrogen and testosterone are nonpolar, they will dissolve in and pass through the membrane.
Label the fluid mosaic model of the cell membrane.
(Aliff drawing)
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Questions to Ponder 1.1.
1. Do a little research and see if you can find diseases of the following membrane channels:
a. Epithelium chloride.
b. Potassium channels in heart tissue.
c. Potassium channels in neurons.
d. Sodium channels.
2. Do a little research and see if you can find diseases of the following receptors:
a. Androgen receptors (absent).
b. Growth hormone releasing hormone (loss of function).
c. Follicle stimulating hormone in females (absent).
d. Thyroid stimulating hormone (gain).
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FLUID COMPARTMENTS IN THE BODY
What would happen if the blood plasma compartment
had more
water/less solutes than the extracellular compartment with less
water/more
solutes? Look up edema.
Types of Transport Between Fluid Compartments
or From Air
to a Fluid Compartment
Cell membranes are semipermeable (selectively permeable). Some small particles, such as oxygen and carbon dioxide, can enter or exit cells using their kinetic energy. The concept of semipermeability can be compared to the way a window screen serves its purpose. The screen is a passive filter, molecules of air and particles of dust may pass through it, flies and mosquitoes cannot. If we modified our screen by giving it an electrical charge, it would repel particles of the same change and attract particles of the opposite charge, then it would be differentially permeable.
{[[[[Figure needed here.]]]]
Living membranes are differentially permeable: certain ions and molecules may enter or exit regardless of their size in many cases. See the sodium/potassium pump following. Generally, those materials pass through the membrane that are lipid soluble, sized appropriately, of the correct electrical charge, or have special channels. Some channels may be passive or actively gated channels in which entrance or exit of molecules is controlled by a gated channel.
Passive transport does not require any output of energy by a living cell. The energy of passive transport is kinetic.
A. Diffusion is the process of transport that uses kinetic energy to move molecules from areas of high concentration to areas of low concentration. All molecules move in straight lines and in random directions. As temperature increases, motion increases. Therefore, more molecules will move from higher concentration areas to lower concentration areas than move from low to high. Since the net movement of particles is from high to low, the particles move "down their concentration gradient." Can something purposeful be accomplished in a random movement? Sure! This is the way oxygen gets from inhaled air to the blood and on to the cells that need it. Carbon dioxide and ammonia wastes depart from cells by diffusion. Remember that the moving molecules do not "know" where they are moving, they just move randomly. Leak channels are passive channels for specific ions such as K+. See the Na/K pump illustration, below.
1. Osmosis is a special type of diffusion in which water moves from high to low concentration areas through a membrane. A semipermeable membrane allows water or other small molecules to pass through because the openings in the membrane are of the proper size. Water molecules are very small and although they are polar, they will pass through the plasma membrane of the cell. Some cells have aquaporin channels that transport water specifically, but passively nonetheless.
Cells may be living in one of three fluid environments, depending on the concentrations of solutes and solvents there.
Terms
of Tonicity
Hypotonic solutions are
characterized by
higher concentrations of water (solvent) and lower concentration of
dissolved
substances (solutes) as compared to another solution - in this case it
is the intracellular
solution of solutes and water that the hypotonic solution is being
compared to.
Freshwater fishes live in a hypotonic environment: this means that the
water
that flows over their gills is less salty than the blood that flows
through the
gills. Which way will the water move? The water is more concentrated
outside
the fish's gills than in the blood inside. Therefore, the concentration
gradient moves water into the blood. The solutes in the fish's blood
generally
stay in the blood. See p. 71-75 of textbook.
If one takes a freshly cut potato strip
and puts
it into pure water, the strip will swell. The same thing will happen to
blood
cells if they are placed into a large amount of pure water. As a matter
of
fact, they will swell and burst.
See fig. 3.9 of textbook.
Slightly hypotonic solutions are used to relieve dehydration. Severe dehydration is not to be treated with large amounts of pure water. This is a problem for nurses as the dehydration after an operation may cause them to demand water. Ice chips are given instead. The problem being avoided is cerebral edema: water moving through the blood-brain barrier into brain tissue will cause sudden swelling and possibly the death of the patient.
2. Hypertonic solutions consist of a higher concentration of dissolved substances and lower concentration of water as compared to another solution. If one places cells in a hypertonic solution, e.g. 2% sodium chloride/L of solution, the red blood cells will shrivel (crenate). Such rough, irregularly shaped red blood cells would not move smoothly through capillaries. Therefore giving an intravenous solution of 2% NaCl would have disastrous effects on the patient. Slightly hypertonic bath solutions are used in kidney dialysis. See the description below.
a. Osmotic Pressure
The pressure developed by water moving from a hypotonic solution towards a hypertonic solution is called osmotic pressure. Osmotic pressure is proportional to the difference in water and solute concentrations between 2 points, in other words, the steepness of the concentration gradient. A general rule is this: naturally, water moves towards higher solute concentrations. Is a dehydrated patient's blood hypertonic to normal saline? Yes! Therefore, a slightly hypotonic solution would be used intravenously to hydrate a dehydrated patient.
Bulk flow of water (solvent drag) accompanies the active transport of solutes. As solutes are moved by cells, water follows the solutes passively.
3. Isotonic solutions are equal in effective concentration of water and solutes inside and outside the cell. Physiological or normal saline consists of 0.85% NaCl in water (8.5 g/L). It is isotonic to blood cells. Why are isotonic solutions of salt and glucose (dextrose I.V. is 5.1% glucose) given to patients? First they increase the patient's blood volume and blood pressure - this gets nutrients to cells and allows for the kidney's to remove waste. The glucose I.V. feeds patients intravenously. An I.V. called Ringer's solution or lactated Ringer's may be given if the patient has electrolyte imbalances, for feeding (the lactated I.V.), or to dilute I.V. injected drugs.
Label the RBCs, as indicated below,
indicating relative amounts of water flow into and out of the
cell (longer arrows means more water flow than shorter arrows).
Solution a.
(left) is hypertonic. B. is hypotonic, c. is isotonic.
Generally, in a solution, one particle of solute has the same effect on osmotic pressure (movement of water through a membrane) as any other solute particle regardless of its molecular weight. If the concentration of solute particles were the same inside a cell and outside a cell, the movement of water would be equal in both directions and the cell's environment would be isotonic.
Label the following diagrams: a. The first two solutions are isotonic. Why? 0.15 M of NaCl actually makes 0.30 M of particles because each molecule of NaCl -à Na+ (+) Cl- ions. B. If you double the concentration of glucose, now it is hypertonic to the 0.15% NaCl and water will move towards the hypertonic solution.
Reverse osmosis is a process used to purify water. A piston is used to press a hypertonic solution against a semipermeable membrane. On the other side is a hypotonic solution. Therefore a physical pressure exceeds the osmotic pressure and the water moves from a low concentration of water to a higher concentration area.
_____________________________________________________________________________________
Why Do This?
What happens when you drink two bottles gallon of "muscle aid" when being a couch potato watching New Year's Day football game? This beverage is loaded with glucose and salts. These solutes, with water following, go into your blood stream. Remember osmosis? If you increase solutes in the blood, water will flow toward those solutes and raise blood volume, then blood pressure goes up. Remember also that in negative feedback homeostasis the input here is an increase in blood glucose, the nervous system is in the black box, and the nervous system arranges for the blood glucose-lowering hormone insulin to be produced. The output is a lowering of blood glucose. What are the effects of drinking alligator beverage over many years as a sedentary life style drink? In studying sugar diabetes, many adult onset D.M patients went through a period of hypoglycemia before they developed hyperglycemia. Why? Here is the sequence of events:
Too much glucose means too much insulin (hyperinsulinemia) and the patient will develop hypoglycemia (low blood sugar). They will feel hunger very soon after eating because their blood glucose is low - it has gone into cells. Over time, the receptors for insulin down-regulate, because there is too much insulin, now the patient develops insulin resistance and usually type 2 N.I.D.D.M. (Non Insulin Dependant D.M.) Diabetes mellitus is the most important single disease in this country because it leads to neurological, cardiovascular and kidney diseases. D.M. is on the increase!
Glucose and salts in beverages are great if you are running and sweating a lot! Otherwise, the principal cause for the increasing obesity and D.M. in the U.S. and Canada is a high carbohydrate, high calorie, and low exercise life style.
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Kidney Dialysis
A dialysis membrane is a plastic, semipermeable membrane that allows most small particles (molecules or ions) to cross in either direction, but large particles are held on one side. For example, the kidney dialysis machine is used to keep a patient alive while her kidneys are healing after an operation or the patient is awaiting a transplant.
There is no urea in the bath solution but particle number concentrations are balanced for ions and glucose. The bath solution used is slightly hypertonic. This increases the osmotic pressure on the blood side, causing water to move into the bath solution. The patients may drink during the procedure to maintain blood pressure. As the water moves, urea molecules follow. Why does the albumin stay in the blood? Can you remove all the urea this way? Kidney patients may have too high or low concentrations of electrolytes. Commonly and particularly if the patient has been overeating fruit, potassium (K+) ions may be too high in the blood. Then the treatment uses a low-potassium bath solution.
In walking (peritoneal) dialysis, the patient
introduces a
sterile bath solution through an opening in the abdominal wall. Urea
filters
into the bath solution from the blood vessels of the abdominal
membranes
(mesenteries and peritoneum). The contaminated bath solution is emptied
daily
and replaced by fresh solution. The patient must be educated to
practice
sterile technique. Infections are common in the area where the tubular
appliance attaches in the abdominal wall. Also, a life-threatening
infection of
the abdominal cavity, peritonitis, is possible.
Facilitated transport (facilitated diffusion) is a passive movement of specific molecules through specific protein-lined channels (permeases) in the cell membrane. Glucose or amino acid molecules will diffuse through specific channels by locking into a gate, causing a change in the shape of the permease protein that then changes shape to allow the glucose to go through. The cell expends no energy: kinetic energy supplies the push for the molecules to go through. Glucose channels (glut-4) in muscle cells are facilitated.
Active Transport is a process used by a living cell that expends ATP energy. Substances can be moved up or against the concentration gradient from low to high concentration areas.
a.
Sodium-Potassium-ATP-ase
Pump - See p. 76 of textbook.
The Na-ATP-ase pump is present in all plasma membranes. It maintains a higher concentration of sodium ions in interstitial fluids as compared to intracellular fluids where Na+ is the most important ion to hold water osmotically. It also maintains a higher level of potassium ions intracellular fluids where K+ is the most important ion osmotically. The Na-K-ATP-ase pump is essential for neuron and muscle membranes where an electrical polarity must be maintained for neurons to generate and conduct electrical impulses. A typical charge for a polarized neuronal membrane (measured from inside to outside, is -0.70 millivolts. A battery has a positive pole and a negative pole: it will generate and conduct electricity. A "dead" battery is one without polarity. Polarity allows for a small bit of electricity (0.1 v for membranes) to be conducted that is necessary for our neurons to communicate with each other and with muscle cells. This process will be described more thoroughly in chapter 12.
The NaK-ATP-ase pump pushes Na+ ions out until there are 10-12 times more outside the cell than inside. Then it pumps K+ ions inside the cell until there are 30 times more K+ inside than outside the cell. When ATP attaches a high-energy phosphate, the ATP-ase (the protein is an enzyme that hydrolyses ATP) protein channel changes shape to move the Na+ out; when the phosphate is removed, the protein gate reverts to its original shape and moves the K+ in. Notice that after this pump runs for a while, the transport of ions is from a low concentration area to an area of high concentration.
Refer to the following diagram:
|
Start - Step 1 - phosphorylation (adding
a high energy phosphate bond) of the protein pump (allows Na+
to attach by changing the shape of the protein. Na+ moves
out) |
Step 3 illustrates leakage channels.
|
Final State - where are most of the
positive ions? Inside or outside? |
|
|
Are the steps 1 and 2 active transport of Na+ ions from low to high or high to low concentration areas? Is this also true for K+ ion movement? The membrane will hyperpolarize if additional cations are moved out or anions are moved inside. |
|
Mutations of the genes that make Na-K-ATP-ase pump proteins of the heart lead to its failure.
Active Transport of Solids and Liquids
Endocytosis is a process that creates membrane bound
vacuoles or
vesicles (endosomes) formed at the cell surface and moved inside. Both
the
formation and movement of these vesicles requires the expenditure of
ATP. The
vesicles will be anchored to microtubules or microfilaments and moved
through
the cell by a ratcheting action described below. Also these vesicles
may or
will float freely in the cytoplasm as it moves (cytoplasmic
streaming). See p. 78 of textbook
Conversely, exocytosis is a
process that moves the contents of vesicles out of cells. The membrane
bound
vesicle will merge with the plasma membrane. Exocytosis occus in
phagocytosis
and when coated fat droplets (chylomicrocrons) are released from
certain cells
lining the small intestine. These fat droplets pass from the
interstitial
fluid, to lymph and on to blood.
Types
of Endocytosis
a. Phagocytosis translates to "cell eating"- solid particles of food like bacteria are engulfed by immune cells called macrophages (translated "big eaters") in tissues or neutrophils and monocytes in the blood. Lysosomes (see below) fuse with a "food" vesicle that is formed and empty their powerful digestive enzymes. A hapless bacterium is digested and its remains are removed by exocytosis.
b. Pinocytosis literally means "cell drinking" - liquids are engulfed into ultramicroscopic vesicles. This is important for the absorption of the products of digestion. In the kidneys, blood volume regulation through the reabsorption of water and solutes from the initial filtrate, and electrolyte balance is assisted by pinocytosis.
c. Receptor mediated endocytosis
- low
density lipoproteins (LDL's, packages of fat and cholesterol)
are taken
into cells by
receptor mediated endocytosis for use in metabolism, production
of
steroid hormones and membrane structure (and if they are taken in by
liver
cells, excretion). This is another lock and key process, the protein in
the
lipoprotein carrier serves as the key and a receptor on the surface of
the
target cell is the lock. Vessicles that form in plasma membrane may be
coated with receptor proteins or not. The most common coating proteins
are clathrin and caveolin. See p. 80-81.
When the liver cells (hepatocytes) process the lipids delivered by the chylomicron droplets, it repackages the fats and cholesterol into lipoprotein carriers. VLDLs (very low density lipoproteins) are large droplets that carry fat and cholesterol in the blood. LDLs and HDLs split off from VLDLs. As compared to VLDLs, LDLs have proportionally more cholesterol than fat.
Some LDLs contain oxidized cholesterol for excretion by the liver, perhaps in a special type of LDL. Although they are normally present in the blood, LDL's are called "bad cholesterol" because of their relationship to coronary artery disease. LDL cholesterols play a role in the development of atherosclerosis, the formation of fat and cholesterol deposits in the walls of the coronary arteries of the heart and other locations. LDLs are engulfed by macrophages that crawl into the walls of arteries through lesions in the cells lining them. Oxidized cholesterol crystals are found in the buildup of fat, cholesterol, calcium deposits and collagen, collectively known as atherosclerotic plaque. Gases in cigarette smoke, viruses or bacteria, may make the lesions in the lining of the vessel that the macrophages crawl through. Also blood clots tend to form on the lesions; therefore, a clot plus the deposits in the arterial wall may block or occlude an artery. First, the heart muscle cells will be deprived of oxygen and nutrients, producing ischemia, and subsequent the heart muscle cells will die and decay, producing a lesion called a myocardial infarct.
Plaque deposits in coronary arteries may block the blood flow to heart muscle. HDL's (high density lipoproteins) are oxidized cholesterol scavengers therefore the "garbage trucks" of the blood. They carry the 'rancid' or oxidized cholesterol and normal cholesterol to the liver to be partially excreted with bile that is mixed into the digestive chime. Some of this cholesterol in bile will be used to emulsify fats, some will be reabsorbed by the small intestines, and some will be excreted in the feces. HDL's are called "good" cholesterol for this reason.
Normally, there is a ratio of LDL/HDL is
2.0
units or less/1. Higher ratios of >3/1 indicate increased risk
for atherosclerosis.
Your total cholesterol measure (<190 is good) is not as good
information as
an LDL/HDL ratio. The former can be done will a simple finger punch and
blood
blot. The latter must be done using blood drawn after overnight
fasting. Anyone
who has an immediate member of
their family die in the twenties or early thirties should have a
fasting blood
work performed by their physician. Heart disease is also related to a
high
intake of saturated fats and even high intake of fats in general, but
inheritance
plays a large role. Hepatocytes are directed by their genes to make a
certain
amount of lipoprotein carriers. But more importantly, genes of many
cells make
LDL receptors that are needed to put LDL-transported fat and
cholesterol into
cells. Familial hypercholesterolemia results from an inherited
genetic
defect in making these receptors.
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Questions to Ponder 1.2
1. If you have seen the classic movie, "The Blob,"
why can't single cells be as large as trucks?
2. Explain how, in a sedentary person, a diet high in simple carbohydrates, animal fat and salts contribute to the increase of diabetes mellitus seen in the U.S. and Canada.
3. Explain what would happen to blood pressure if the osmotic protein albumin was depleted by liver failure.
4. Criticize the media-invented term 'bad
cholesterol' for
LDL's.
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Membrane Bound Organelles - See p. 84 of text.
The term organelle for cells means "little organ." The nucleus is a large organelle covered by a double envelope of membrane that has small, single layered nuclear pores that allowing the passage of materials into (steroid hormones) and out (messenger RNA). The nucleus contains DNA either in thin strands or thickly coated with proteins as dense chromatin. The DNA contains the "messages of heredity" which dictate when and what the cell is to do or make. It is analogous to a master computer in a factory's main office that contains a library of blueprints and instructions for making different products. A nucleolus is a dark spot inside the nucleus that contains dense chromatin necessary for making ribosomal RNA and associated proteins. Before cell division (mitosis, see below) there are two nucleoli per cell, immediately after cell division there is one.
The Cell Factory at Work
Let's consider the beta cells in the endocrine glands of the pancreas, the islets of Langerhans. Beta cells possess genes that direct the synthesis of the protein hormone, insulin. As we discussed in chapter 2, a gene with its DNA triplets can be transcribed into a messenger RNA polymer.
The Steps of Transcription
1. The double stranded DNA will separate into two strands when the enzyme DNA gyrase breaks the hydrogen bonds, holding the nitrogenous bases together in a "rung" of the DNA ladder.
2. The enzyme RNA polymerase will join the appropriate reciprocal nucleotide to an exposed nucleotide on the strand to be copied - the sense strand. Remember that the A in a DNA triplet will bind to a U (uracil) in an mRNA nucleotide because RNA does not have T (thymine). So the DNA triplet ACT will transcribe to the mRNA codon UAC in messenger RNA. Please review the binding rules in chapter 2.
The Steps of Translation
1 The messenger RNA polymer formed, after some modification described in chapter 29, will leave the nucleus by moving through the single layer of membrane covering a nuclear pore. The modified mRNA is a copy of a gene or "blueprint" of the insulin product to be made by the cell factory.
2. The mRNA will attach to the small subunit of the ribosome, the "assembly line" of the cell factory. At this time the large subunit will join the complex. Ribosomes are made of ribosomal RNA and protein; they are the location of protein synthesis. Ribosomes may be "free" in the cytoplasm or adherent to the endoplasmic reticulum, a stack of hollow membranes, appearing much like a deflated balloon that has been folded.
3. Transfer RNA (tRNA) can pick up certain amino acids. There are 61 types of tRNA that can carry 20 amino acids. We will explore this aspect further in chapter 29. The catabolism of ATP charges each amino acid with the energy to make a bond with its tRNA. Transfer RNA has anticodons that bind reciprocally to the mRNA codons at the ribosome. Therefore the codon AAA will bind to the anticodon UUU. The amino acids then undergo dehydration synthesis, forming peptide bonds using the energy that originally came from ATP.
4. When all the codons have been translated, the mRNA will disassociate from the ribosome, and its small and large subunits will separate.
Endoplasmic
Reticulum
There are two types:
a.
Rough endoplasmic reticulum (rER) has ribosomes
attached to its outer surface and it stores the proteins made at the
ribosome. The first protein to be made
is not the final product, but preproinsulin that is a larger
molecule.
The pre- portion is a nonpolar "leader" sequence of amino acids that
allows the protein to penetrate the largely nonpolar outer membrane of
the rER.
An enzyme inside the ER will cleave the pre- portion forming proinsulin.
The endoplasmic reticulum forms transport vesicles by a process that resembles the "budding" of yeast cells. A bubble-like structure will form from the ER membrane and detach. This transport vesicle is therefore a membrane-bound "fork lift" that carries proinsulin to the Golgi apparatus
b. Smooth endoplasmic reticulum (sER) is associated with the production of polysaccharides (glycogen) or lipids. Glycogen crystals form adjacent to the sER.
The Golgi Apparatus - see p. 87
The Golgi is similar to the endoplasmic reticulum, but it is larger and always smooth. It mixes enzymes with the collected proinsulin to be exported in larger secretion vesicles that bud off the outer trans face. Like "delivery vans," the secretory vesicles head from the factory warehouse to the distributor. Along the way, the pro- portion is cleaved. The secretory vesicles merge with the plasma membrane and deposite their final products (insuilin and the pro- sequence of amino acids) by exocytosis. The insulin made by our cell factory cell is now in the extracellular fluid and moves on to the blood to be distributed to target cells.
Lysosomes
Lysosomes are the so-called "suicide bags" of the cell. They form by budding from the Golgi apparatus. They are filled with a variety of enzymes that could destroy (hydrolyze) most materials in the cell. In fact, when cells die, these lysosomes burst and the cell undergoes autolysis (breaks itself down). When the amoeboid immune cells (macrophages and neutrophils) ingest bacteria or cell debris, lysosomes merge with a "food" vesicle made in phagocytosis and lyse its contents. Lysosomes can also take in and break down used organelles such as mitochondria. In the cell factory, lysosomes are "vacuum cleaners."
In Tay-Sachs disease, an enzyme needed to break down certain neuronal membranes is absent because the genes that produce it are mutated. The cells then fill up with lysosomes filled with membrane layers. This is similar to fill garbage bags in your house without the ability to remove them. Imagine being limited in moving around your house!
Tay-Sachs is one of several storage diseases of cells that occur when one of the many lyosomal enzymes are absent. Certain useless materials in the lysosome build up instead of being normally broken down and the materials recycled. Brain cells will gradually cease to function. Typically the baby is normal at birth, but then does nor progress in learning, eventually the child becomes vegetative and dies. There is no current treatment for TSD but the genes that produce the condition can be identified in the cells shed by a fetus. Other inherited lysosomal storage diseases, such as Gaucher's and Fabry's, may cause signs ranging from short stature and mental retardation, to kidney failure, stroke ere is no current treatment for TSD but the genes that produce the condition can be identified in the cells shed by a fetus.
In a miner's disease
called
silicosis and in asbestosis, mineral crystals may puncture lysosomal
membranes,
causing its enzymes to leak out into the cytoplasm. Lysosomal leakage
is also
implicated in rheumatoid arthritis and hypervitaminosis A (vitamin A
weakens
the membrane). Steroidal anti-inflammatory drugs strengthen lysosomal
membranes
and prevent leakage.
Peroxisomes
Peroxisomes are similar to lysosomes in that they are vesicles covered by a single membrane that encloses enzymes. However, they do not contain DNA and can replicate by a simple enlargement and division. The peroxisome's 14 enzymes include oxidases and peroxidases (e.g., catalase). The superoxide (peroxide) free radicals (see chapter 2), by-products of the oxidases, are detoxified there. Peroxisomes have a role in the catabolism (beta oxidation) of long chain fatty acids and the anabolism (synthesis) of cholesterol and the steroid hormones and bile acids derived from cholesterol. Inherited disorders include enzyme deficiencies (or lack thereof) and structural abnormalities that are metabolic in nature. Peroxisome enzyme deficiency is one of many causes of "failure to thrive" in infants. Refsum disease is an inherited enzyme deficiency that causes cerebral ataxia (unsteadiness) and loss of vision (retinitis pigmentosum). Phytanic acid, a common fatty acid in vegetables and dairy products, builds up in cells due to the absence of an enzyme that lyses it.
The Cell as a Factory
Mitochondria
Mitochondria are the "powerhouses" of the cell. The ATP molecules made there are used for many activities including anabolism of proteins, lipids and carbohydrates; active transport, and cell movement. There are over 1000 mitochondria in an average cell. The mitochondrion has two membranes, an inner and outer. Anaerobic reactions occur just outside the mitochondrion. The reactions of the oxidative cell respiration (Kreb's Cycle) occur near and in the inner membrane. Most ATP is produced aerobically. Folds called cristae occur on the inner membrane. All mitochondria have DNA and all come from the mother's oocyte.
Mitochondria are self-replicating. So far 13 genes have been discovered in mDNA: mutations of those genes cause mitochondrial cytopathies. One rare type of epilepsy results from a mutation of mitochondrial DNA. Epilepsy is an "electrical storm" of the brain. Neurons there depolarize and send electrical messages. If there are too many depolarizations, coupled with a lack of neural inhibition, over stimulation of the brain causes a loss of consciousness. Another mDNA mutation causes Leber's optic neuropathy that causes blindness.
Cytoskeleton
A system of microtubules, anchoring proteins, myofilaments and the gel state of the cytoplasm allows a cell to have shape. The microtubules and myofilaments participate in movement of the whole cell and certain organelles. See below.
Microtubules
Microtubules assist in
cell reproduction by moving and
positioning chromosomes (containing DNA).
Microtubules are composed of helically stacked tubulin protein
molecules
(polymers) to form multimers. Some microtubules have dynein or
kinesin
arms that are motor proteins that can ratchet in opposite directions. These motor proteins attach to and push
(ratchet) an adjacent microtubule in the opposite direction. The
ratcheting is
powered by the hydrolysis of ATP.
If the adjacent microtubule has an organelle or other structure
attached
to it (e.g., a chromosome), then the structure will appear to be moving
in the
cell. Moving vesicles are coated with motor proteins, so the organelle
appears
to be "walking" down a microtubule. We can think of some microtubules
as being intracellular "highways."
http%3A%2F%2Fcellbio.utmb.edu%2Fcellbio%2Fmicrotubule_structure.htm
[[[[Drawing needed.]]]]
In
the cell division of animal cells, microtubules "grow" from protein
clouds immediately surrounding a bundle of nine triplets of
microtubules (a 9 +
0 arrangement) collectively called a centriole. The protein cloud is
called a
microtubule organizing center or MTOC. After cell division, these
microtubles
disassemble. Some anticancer and other drugs, e.g., colchicines and
taxol,
interfere with the making or disassembly of microtubules, respectively.
The
result is a halt to the process of cell division. See below.
http%3A%2F%2Fcellbio.utmb.edu%2Fcellbio%2Fmicrotubule_structure.htm
Intermediate
Filaments
Protein
intermediate filaments are smaller than microtubules and contribute to
a stable
cell shape. They consist of a multimeric complex of tetrameres, four
units that
contain 4 protein helices to make a total of 16 helices per
intermediate
filament.
[[Insert
drawing similar to:
Of
many kinds of the "thick" filaments, we will discuss lamins, GFAPs,
neurofilament proteins, keratin, vimentin and desmin.
Mutations of lamin genes result in a shortening of lamin
fibers seen in cardiomyopathy.
Lamins
help hold the nucleus in
place and
line the inner nuclear membrane. Lamins dissolve in prophase (see
below), when the
nuclear envelope dissolves, and reassemble in telophase, when the
nuclear
envelope reforms. Mutations of the
lamin-A gene on chromosome #1 cause aging disease (progeria) in
children.
Children usually die at age 13 of a heart attack or stoke. The
defective gene
results in a mutated, shortened lamin protein. As a result, progeric
cells have
lumpy, malformed nuclei. Also progeric chromosomal telomeres are
abnormally
short (see below). Either way, mitosis is affected.
(photo
of progeric child and cells.))
|
|
redraw??
ref: http://www.geneseo.edu/~mab5/edpage.html
GFAPs are found in glial cells of the brain.
Too much GFAP
production occurs in the cancer cells resulting from mutations of the
genes
that control GFAP production. Also when GFAP gene activity is
over-expressed,
globules of GFAP are found superimposed on the neurofibrillary tangles
and
plaques seen in Alzheimers disease (AD) neurological tissues.
Neurofilament
protein is another category
of
intermediate filament. These
channel the growth of the thinner, cable-like distal extensions of
neurons
called axons. They also aid in axonal transport. The genes that produce
neurofilaments are over-expressed in Parkinson's disease and
the plaques
amyotrophic lateral sclerosis (ALS: Lou Gehrig's disease).
(((Cell
with florescent stain of neurofilaments.
Several
types of keratin fibers fill up cells in the glassy layer of
the skin
(stratum lucidum). Above this layer, the cells are dead and scaly.
Therefore, the
upper layer of skin is called keratinized. There is an
uncontrolled,
over-expression of the genes that make keratin in many cancer cells. Psoriasis
is a skin disease due to the cross-linking of keratin proteins.
Vimentin is an intermediate fiber found in the soft
tissue
cells - muscle, connective and neural. Vimentin filaments play a roll
in the
transport of cholesterol to the organelles involved in the synthesis of
steroid
hormones. The over-production of vimentin is a maker for soft tissue
tumors.
Desmin
is a protein filament found
in muscle
cells. The desmosome is a structure that binds cells together. Shown
below is a
desmosome that binds cardiac muscle cells together.
Microfilaments
Microfilaments are much smaller than microtubules. They consist of the contractile proteins actin (thin myofilaments) and the larger myosin (thick myofilaments) that are found in great abundance in muscle cells where they are called myofilaments. Actin and myosin aid in cell movements and in the "pinching off" (cytokinesis) of two daughter cells in cell division. Myosin has ATP-ase "heads" that ratchet against the globular proteins in actin. See below. We will take this subject up in greater detail in chapter 10.
See a French site of cell animations that
include actin
and myosin ratcheting at http://www.biomultimedia.net/archiv/muscle.htm
Locomotor
Organelles
Locomotor organelles
move cells such as sperms and they move
mucus and cleaving embryonic cells on the surfaces of the respiratory
and
reproductory tracts, respectively.
1. Cilia
Cilia are numerous
organelles covering most of the cells of
the respiratory tree, the female Fallopian
tube
and some protozoa such as Paramecium. Cilia push dust and
microbe
contaminated mucus out of the lungs. Cilia have a whip like beating
action and
an inner "9+2" pattern of microtubules. Movement is accomplished by
the ATP powered attachment of dynein arms of one outer
microtubule pair
to an adjacent pair, the dynein arms then pulling down "like climbing a
ladder." At the origin of each cilium is a basal body, in which
a
9-pointed star shaped protein called centrin lies proximal to
the 9+0
group of microtubules. The inner two microtubules appear distally. The
basal
body includes an MTOC and the centrin may serve the same function as
the bundle
of microtubules in the centriole. It resembles growing large crystals
starting
with a tiny "seed crystal."
llustration.
The
arrow in d indicates the centrin protein.
http://www.molbiolcell.org/cgi/content/full/14/7/2999/FIG3
When lungs are damaged by long-term inhalation of polluted air, such as cigarette smoke; the cilia that cover the cells lining most of the lung passages disappear. One of the first signs is a characteristic vigorous morning-cough that functions to remove secretions trapped in the bronchioles. These secretions limit flow of air to the air sacs where oxygen moves into the blood and carbon dioxide moves into the air to be exhaled. The smoker's hacking cough occurs in the day when they are smoking. This is caused when nicotine paralyses the cilia of the respiratory tree.
2.
Flagella
Flagellae are whip-like structures that similar to structure to cilia, but larger. Some protozoan flagellae move with a corkscrew action and some with a propeller action. Prokaryote flagella have no microtubules.
Each sperm cell has one flagellum that moves in a propeller (rear) fashion. Distal to the head of the sperm is a mid-piece containing mitochondria that power the ratcheting of motor proteins arms as described above. If the genes that make dynein or kinesin are mutated, cilia and flagella will not function. For flagella, this would cause sperm cells to be immotile. For cilia, such a mutation results in the absence of motor proteins and primary ciliary dyskinesia (PCD), characterized by chronic pulmonary obstruction and infection.
3. Pseudopodia
Pseudopodia are the
"false feet" that an amoeboid
cell extends to capture "food." They may be fine, narrow extensions
of the cell or more broadly shaped. Remember that the cytoplasm of
colloidal mixtures
of proteins in macrophages can
undergo changes
of state from a liquid sol stage to a semi-solid gel stage and
accomplish
movement. The cell extends a pseudopod by converting the interior of
the
extended arm to a gel while liquefying the trailing portion into a sol.
A
second reversal back to sol occurs at the leading edges of the
pseudopod and
sends sol streaming to the rear of the cell. These reversals of state
(sol-gel)
are controlled by pH changes and ATP powered movements of
microfilaments.
_________________________________________________________
Questions to Ponder 1.3
1. An antibiotic, Rifampicin,
binds to the
ribosomes of bacteria irreversibly. Would the bacterium die
immediately?
Describe the processes in the bacteria that would be affected.
2. The organism that causes
amoebic
dysentery moves by extending one large pseudopodium and can be observed
with
red blood cells inside it. Describe its movement and what happens to
the red
blood cells.
3. Describe a storage disease
involving
microtubules.
________________________________________________________
CELL DIVISION
Mitosis Overview - See p. 102 of text .
Mitosis is a form of cell division that is accomplished in one division: one cell divides into two daughter cells. Mitosis is the most common form of cell division: it is used for replacing cells in organ such as the skin and stomach lining that constantly shed old cells. Some tissue cells lose the ability to do mitosis, generally speaking; e.g., neurons, skeletal muscle and cardiac muscle cells. The liver is an internal organ that can replace its hepatocytes after a disease like hepatitis. When the sperm cell fertilizes an egg, the resulting zygote begins the fist stage of the cell cycle, G1. The dividing cells then will eventually produce a baby and a full growth adult.
First it is important to understand that, expecting cancer cells, most of an average cell's life is spent in activities other than mitosis. This is reflected in the cell cycle.
The Stages of the Cell Cycle
1. G1 is the first growth and metabolic stage. It occurs after cell division, immediately following mitosis. It we use the example of a hapatocyte, then this cell is doing its normal functions. It energy and gene activity is causing the hepatocyte to make bile and detoxify certain chemical wastes. In G1 the DNA strands are single. The 46 single chromosomes (a single double helix of DNA) of a human cell cannot be seen with the light microscope.
2. The S phase follows G1. DNA synthesis and replication forms a second strand of DNA on a template or conserved strand. A double chromosome is formed. See chapter 2 and below.
3. G2 is a second growth and metabolic stage; it immediately precedes mitosis. DNA strands are double in anticipation of distributing one set of genes to each daughter cell.
Notice that mitosis is only a small part of the cell cycle. G1, S and G2 are also referred to an interphase.
Chromosomes
Chromosomes are complexes of highly coiled DNA surrounded by
proteins that
cannot be seen in entirety with the light microscope until the prophase
of cell
division. Chromosomes get shorter and thicker as prophase continues.
The DNA
forms tight coils and loops around the histone proteins; other
proteins,
the nonhistones, form a covering of the coils and loops. The double
chromosome consists 2 strands of DNA joined by a single
centromere. Double
chromosomes are always present in mitotic prophase and metaphase
(see
below). The centromere consists of 2 MTOCs called kinetochores. A single chromosome has one
centromere. The rule for counting chromosomes is to count centromeres,
so one
double chromosome is one indeed. Each strand of DNA is called a
chromatid.
A double chromosome.
Karyotype
The human karyotype is a chart of the 23 pairs of chromosomes in a typical somatic or non-sex cell nucleus. White blood cells are cultured and arrested in late prophase of mitosis by the chemical colchicine that prevents microtubule formation. The pairs numbered 1 to 22 are call autosomes, pair number 23 are called sex chromosomes. There are two X chromosomes for a female and X and y (much smaller) for a male. When the chromosomes are stained, bands are displayed which help sorting the chromosomes correctly. Also the length of the chromosome and the position of the centromere are taken into account.
The two members of a pair are called homologous, meaning similar in structure. Genes that make certain proteins will occur in the same linear order normally in both homologous chromosomes. To illustrate, we will assume that we have two homologous single chromosomes. One chromosome can be referred to as paternal as it comes from the father of the individual from whom the cultured cells was taken. The matching homologous chromosome is called maternal. Normally if there is a genes for making enzyme a on one end of a homologous chromosome, an enzyme b-making gene in the middle, and an enzyme c-making gene on the other end, there is be a matching set of a, b and c genes on the homologous chromosome in the same linear order and in the same geographical position. Remember that if both a genes are mutated, then its enzyme product will not be produced and the individual will have an inherited illness such as lactose intolerance.
Flourescing chromosomes in karyotypic arrangement at left, unarranged at right
Types and Stages of Cell Division
Fission
Bacteria can reproduce by replicating a single chromosome, sending each strand resulting into a daughter cell. This is similar to cloning in that usually the chromosomal genes are identical in both daughter cells. Bacteria have other genes in small loops of DNA called plasmids. You will learn how bacteria can do a form of sexual reproduction using these plasmids in a microbiology course.
Mitosis in Diploid Cells - See p. 102-103.
Diploid cells have two sets of chromosomes, a paternal and a maternal set. Mitosis requires only one cell division and the chromosome number stays the same from generation to generation.
<>Phases of Mitosis1. Prophase initiates cell divison. Human somatic cells always begin prophase with 46 double chromosomes.
Steps
a. Prophase begins when chromosomes become visible as they thicken and shorten. The DNA molecules become coiled and tightly would around histone proteins and become coated by non-histone prtoteins. At this time the chromosomes are visible when viewed with the light microscope.
b. Each centriole doubles in s phase to form a centrosome. The centrosome splits and the two resulting centrioles migrate to opposite poles of the cell. As the microtubules grow, the two centrioles are pushed away from each other.
[[[Image needed.]]]
3. The nuclear membrane disintegrates.
4. Microtubules form at the kinetochores and at the protein cloud surrounding the centriole - both are MTOCs. There are three types of microtubules directly involved in cell division:
a. Centromeric (kinetochore) MTs extend from the centriole to the centromere.
b. Polar MTs extend from centriole to centriole, crossing over the jumbled chromosomes to enclose a "spindle" of MTs.
c. Anchoring MTs (old = aster fibers) maintain the polar position of the centrioles by attaching to anchoring proteins in the plasma membrane.
<> 2. Metaphase occurs when the double chromosomes are lined up across the equator of the cell.3. Anaphase: The Push-Pull Analogy
a. Polar microtubules appear to lengthen and thus their ratchetings push the opposite poles of the cell away from the center, this effect typically increases the diameter of the dividing cell from pole to pole. Polar microtubules assist in the push through the ATP-powered ratcheting action of motor proteins on adjacent polar microtubules.
b. The MTOC, the pericentriolar protein cloud can assemble the tubulin proteins of microtubules and thus lengthen them by assembly or shorten them by disassembly.
c. The centromeric M.T.s
apparently shorten
and pull the single chromosomes to each pole. Anaphase
is easily
recognized by the separation of the double chromosomes to make single
ones. For the human liver cell, 46 d (double) chromosomes
divide
and 46 s (single) chromosomes go to each pole.
4. Telophase is recognized by the reforming nuclear membrane around the cluster of single chromosomes moved by microtubule ratcheting. Cytokinesis may begin in anaphase: this process pinches off the "waist" of the cell at the site of the former equator of the cell if the cell division is equal.
Chromosomes
Chromosomes are complexes of highly coiled DNA surrounded by proteins that cannot be seen in entirety with the light microscope until the prophase of cell division. Chromosomes get shorter and thicker as prophase continues. The DNA forms tight coils and loops around the histone proteins; other proteins, the nonhistones, form a covering of the coils and loops. The double chromosome consists 2 strands of DNA joined by a single centromere. Double chromosomes are always present in mitotic prophase and metaphase (see below). The centromere consists of 2 MTOCs called kinetochores. A single chromosome has one centromere. The rule for counting chromosomes is to count centromeres, so one double chromosome is one indeed. Each strand of DNA is called a chromatid.
A double chromosome.
Karyotype
The human karyotype is a chart of the 23 pairs of chromosomes in a typical somatic or non-sex cell nucleus. White blood cells are cultured and arrested in late prophase of mitosis by the chemical colchicine that prevents microtubule formation. The pairs numbered 1 to 22 are call autosomes, pair number 23 are called sex chromosomes. There are two X chromosomes for a female and X and y (much smaller) for a male.
When the chromosomes are stained, bands are displayed which help sorting the chromosomes correctly. Also the length of the chromosome and the position of the centromere are taken into account.
The two members of a pair are called homologous, meaning similar in structure. Genes that make certain proteins will occur in the same linear order normally in both homologous chromosomes. To illustrate, we will assume that we have two homologous single chromosomes. One chromosome can be referred to as paternal as it comes from the father of the individual from whom the cultured cells was taken. The matching homologous chromosome is called maternal. Normally if there is a genes for making enzyme a on one end of a homologous chromosome, an enzyme b-making gene in the middle, and an enzyme c-making gene on the other end, there is be a matching set of a, b and c genes on the homologous chromosome in the same linear order and in the same geographical position. Remember that if maternal and paternal a genes are mutated, then its enzyme product will not be produced and the individual will have an inherited illness such as lactose intolerance.
A karyotype is used to confirm the
diagnosis of
genetic diseases caused by gross chromosomal abnormalities. If three #
21
chromosomes are present, Down syndrome is indicated. Also chromosomes
may have
deletions or additions of genetic material that are observable. See p.
1147 of text.
Flourescing chromosomes
in karyotypic
arrangement at left, unarranged at right.
Types and Stages of Cell Division
Bacteria can reproduce by replicating a single chromosome, sending each strand resulting into a daughter cell. This is similar to cloning in that usually the chromosomal genes are identical in both daughter cells. Bacteria have other genes in small loops of DNA called plasmids. You will learn how bacteria can do a form of sexual reproduction using these plasmids in a microbiology course.
If bacteria can divide every 20 minutes, starting with one Salmonella (food poisoning), bacterium, how many would be present in your small intestine in 12 hours?
Phases of Mitosis
Prophase initiates cell divison. Human somatic cells always begin prophase with 46 double chromosomes.
Steps
1. Prophase begins when chromosomes become visible as they thicken and shorten.
2. A centrosome
splits,
the two resulting centrioles migrate to opposite poles of the cell.
Each centriole
doubles after G1 to from a centrosome. See www.cellsalive.com/
3. The nuclear membrane disintegrates.
4. Microtubules form at the centrioles and the kinetochores. There are three types:
a. Centromeric MTs extend from the centriole to the centromere.
b. Polar MTs extend from centriole to centriole, crossing over the jumbled chromosomes.
c. Anchoring MTs
(old
aster fibers) maintain the polar position of the centrioles through
anchoring
proteins in the plasma
Draw Prophase - Include microtubules, centrioles and use 4 double
chromosomes.
Metaphase: double chromosomes line up across center of cell.
Draw Metaphase:
2. Metaphase occurs when the double chromosomes line up
across
center of a cell.
Draw metaphase:
3. Anaphase: The Push-Pull Analogy
a. Polar microtubules appear to lengthen and thus push the opposite poles of the cell away from the center, this effect typically increases the diameter of the dividing cell from pole to pole. Polar microtubules assist in the push through the ATP-powered ratcheting action of motor proteins on adjacent polar microtubules.
b. The MTOC pericentriolar cloud can assemble the tubulin proteins of microtubules and thus lengthen or shorten them by disassembly.
c. The centromeric M.T.s
apparently shorten
and pull the single chromosomes to each pole. Anaphase
is easily
recognized by the separation of the double chromosomes to make single
ones. For the human liver cell, 46 d (double) chromosomes
divide
and 46 s (single) chromosomes go to each pole.
Draw Anaphase:
4. Telophase is recognized by the reforming nuclear membrane around the cluster of single chromosomes moved by microtubule ratcheting. Cytokinesis may begin in anaphase: this process pinches off the "waist" of the cell at the site of the former equator of the cell if the cell division is equal.
Draw Telophase:
MEIOSIS - see page 1078//1071-1075, fig. 28.6//27.5 and 27.8.
The reason why sexual reproduction is seen in protozoa, algae and higher creatures is because it increases the genetic variety of the offspring. Every person carries some mutated genes. Reproducing with an unrelated mate will decrease the likelihood of those mutated genes from being expressed. Generally speaking, genetic outbreeding produces healthier offspring than inbreeding.
Meiosis is a form of cell division that prepares sex cells for fertilization. It is accomplished in two divisions and it reduces the chromosome number by 1/2. The definitions of phase of cell division are approximately the same as for mitosis, expect that the first division is designated meiosis I, and the second, meiosis II.
Spermatogenesis
a. The first division of meiosis is called the "reduction division" because the chromosome number is reduced by one half. In other words the one primary spermatocyte divides into 2 secondary spermatocytes, but the 2 resulting cells have 23 double chromosomes (in human) rather than the somatic cell content of 46. Meiosis must occur previous to fertilization in sexual reproduction. Why? Because the egg contributes 23 s and the sperm contributes 23s. That gives the baby 46s to begin G1 of embryonic development (cleavage).
To illustrate the process generally, we will consider the formation of sperm - spermatogenesis. Cells reside in the testis that can do mitosis or meiosis. The mitosis of spermatogonia ("sperm eggs") is the reason why men can make sperms from puberty to old age. However, in metaphase of the first meiotic division (metaphase 1), 46d chromosomes of the primary spermatocyte divide into 23 d in each of two secondary spermatocytes.
b. In metaphase of the second division
(metaphase
II), 23s chromosomes are distributed to each spermatid that
later
develops into a sperm cell. This is actually a mitotic division. Why?
The
chromosomes number stays the same. We will take this up in more detail
in
chapter 27.
Oogenesis
See pg. 1078-81, 1095//1075 and 1088.
The meiotic formation of eggs or ova is a process of unequal cell division. The reduction division of the primary oocyte produces a large cell and a small first polar body. The first polar body is essentially a sac of 23d chromosomes that has to be jettisoned. The secondary oocyte likewise divides mitotically but equally, producing a mature oocyte and a second polar body of 23s chromosomes. The reason for the "wasting" of chroosmes is two fold: 1. The oocyte must keep its large size because it must contain all the cell organelles and energy to allow it to divide and survive for 6 days. At that time, a blastocyst, consisting of hundreds of cells but no larger than the original zygote, will implant in the lining of the uterus.
SPERMATOGENESIS VS. OOGENESIS
|
Oogenesis unequal cell division
|
Spermatogensis equal cell division
|
|
m-RNA genes, stored energy resources, organelles for the zygote 23 chromosomes all oocytes get large the larger x chromosome |
No organelles contributed 23 chromosomes, half of sperms get |
What would happen to the chromosome number of your great
grandchildren if
meiosis did not occur?
See the illustration below.
FERTILIZATION
Crossing Over
Parts of maternal and paternal chromosomes will break and rejoin to
form new
combinations of genes for the sex cells. This further increases the
genetic
diversity of offspring. Crossing
over occurs in prophase I of meiosis after homologous chromosomes
pair-off
in synapsis. A pair of homologous double chromosomes is called a
tetrad.
When the tetrad separates in diakinesis, parts of the individual
strands
of DNA or
chromatids will break off and rejoin an adjacent chromatid from
the
opposite (maternal or paternal) chromatid.
_____________________________________________________________________________
Questions to Ponder 1.4
1. If bacteria can divide every 20 minutes, starting with one Salmonella (food poisoning) bacterium, how many would be present in your small intestine in 12 hours, assuming none die during that time?
2. For the following stages of mitosis and the cell cycle, fill in the correct number of chromosomes. Designate each set as 46 d or 46 s (double or single) as for a human skin cell. Remember to count chromosomes, count centromeres.
Prophase: ________________
Metaphase: _______________
Anaphase: ________________ (2 groups of ____ and ____ chromosomes)
Telophase: _______________ (as above, in each potential daughter
cell)
G 1 : ______________________
s: _______________________
G 2 : ______________________
Prophase: ________________
3. For the following human spermatogonium and the spermatocytes
derived from
it, designate the chromosome numbers (d
or s) for each stage.
Prophase I: ____________________ (Primary Spermatocyte)
Metaphase I: ___________________...................................
Anaphase I: ____________________ (in each daughter cell to be)
Telophase I: ___________________ (in each daughter cell to be)
Prophase II: ___________________ (Secondary Spermatocyte)
Metaphase II: __________________
Anaphase II: ___________________ (in each daughter cell to be)
Telophase II: __________________ (in each daughter cell to be)
Mature Sperm Cell: _____________
Mature Ovum: ___________________
Zygote = Sperm # + Ovum # = ____________________ (G1 cell
cycle phase of zygote)
4. What would happen to the chromosome number of your great grandchildren if meiosis did not occur?
5. Explain the following statement: "Mitochondrial cytopathies are
always passed from mother to child."
_____________________________________________________________________
For an online learning program on mitosis the Biology Project - Cell
Biology
from the University of Arizona, go to http://www.biology.arizona.edu/cell_bio/cell_bio.html
.
Causes
of DNA/Gene Mutation
1. Radiation - gamma rays, X-rays, ultraviolet rays, beta-rays (electrons) and neutrons can make abnormal nucleotides and bonding patterns in DNA. Specifically, UV-B makes bonds between thymine bases (thymine dimers) that are adjacent "vertically" in the DNA ladder. Beta rays and neutrons are also mutagenic.
2. Viruses insert their DNA or the DNA made from viral RNA into the chromosomes of their host cell. If a viral genome (assortment of genes) is inserted into a human chromosome, oncogenes may result. Most oncogenes are mutated forms of tumor suppressor genes that control mitosis, e.g., BRCA 1 and 2, or genes that cause apoptosis of abnormal cells expressing mutations. Inherited mutant genes can result in cancer include mutant BRCA-1 and -2 that greatly increase the risk of breast cancer, the retinoblastoma gene, and the mutant p53 that is implicated in most cancers including colon and cervical. It is possible that x-rays can precipitate the final mutation of some oncogenes. Here inheritance of a defective BRCA plays a role. Most mutations that produce disease are actually a series of mutations. One study showed that stage 2 brain cancer cells had fewer mutations than stage 3 cells, and so for stage 4. The k-ras mutation is stimulated by estrogen that acts as a mitogen to increase the rate of mitosis of tumor cells. Viral genes that are considered proto-oncogenes include proto-abl, -ras and -onc.
The normal p53 gene causes cells to die if they are too old or are defective. When cells expire, they burst open, hence the name for the process is apoptosis. However, cancer cells are immortal. There are worldwide cultures of breast cancer cells taken from a woman who died of breast cancer in 1968 - they are still thriving as long as the cultures are fed and cleaned.
The National Institute of Environmental Health Sciences and the National Toxicology Program recognizes viruses as carcinogens. These include Hepatitis B and C that cause liver cancer, and human papillomaviruses that cause cervical cancer.
3. Mutagenic chemicals - polycyclic aromatic hydrocarbons (benzopyrenes: MeIQ, MeIQx, and PhIP), the benzene that is in high test gasoline, asbestos, PCBs and PCPs, and vinyl chloride are notorious carcinogens. Diethylsylbestrol was a synthetic estrogen used in the 1960s and 1970s to treat post-menopausal estrogen deficiencies. It not only caused cervical cancer in the women that took it, but also their children. Benzopyrenes are liquids that can be distilled from the smoke of cigarettes, grills, and other incompletely combusted organic hydrocarbons. In the 1960s, benzopyrenes were used to cause tumor growth on the skin of experimental animals. The National Toxicology Program recognizes smoked and smokeless tobacco as carcinogens. In the 1970s, vinyl chloride caused liver cancers in many workers in facilities that manufactured vinyl for plastics.
Mitogens are substances that increase the rate of cell division. Nicotine is not a mutagen, but it is a mitogen. Mitogens such as nicotine, testosterone and estrogen increase the frequency of mistakes in copying DNA and/or increase the number of mutant genes in the resulting cells. The steroid hormones estrogen and testosterone are, respectively, mitogens for breast cancer cells and prostate cancer cells.
4. Mistakes in replication of genes/DNA: Indirectly, increasing the rate of mitosis of cells can lead to mutations that could cause cancer. When physicians observe hyperplasia (abnormal growth) in normal tissues, they consider the condition to be "precancerous." Asbestos and wood dust (surprisingly) are carcinogens but the mechanisms of mutation are not definitely known. However since these provide a constant irritation that produces hyperplasia, the mutagenic effect certainly includes mistakes in replication. Synergism (interaction) with other mutagens may also be a factor.
Aging of Cells
[[[[from Art Explosion]]]]
The Causes of the Aging of Cells
Programmed cell death and malfunctions occur during aging.
For cells the causes of aging include:
1. Programmed cell death and malfunctions are natural processes. Also viruses can cause changes in cells that lead to their normal self-destruction by apoptosis. Why do humans live 70+ years and dogs only 12+? It is certainly not because dogs don't get enough sleep!
The current theory asserts that there is a gene-controlled limitation on the number of times a given cell can do mitosis (the Hayflick limit), although there are fibroblast cells that may have unlimited potential. One problem with the gene-limit to cell division is that the number of divisions that cultured cells undergo generally exceeds the life span of the organism from which the cells were taken. Also when older cells are moved into younger organisms, they divide normally and the life span of the recipient is not shortened.
But genes are
certainly involved in
aging even if we don't understand very well how they produce declining
functions such as endocrine hormone secretion.
2. Accumulation of mutations from background radiation, radioimaging, chemical exposure, and mistakes in replication will cause cells to
age and cell metabolism accordingly slows; e.g., the velocity of neuron conduction slows with advancing age. A theory that blends with this one, suggests a decline DNA repair functions. If the genes for making the enzymes that repair DNA are mutated, then the repair function will be affected. The accumulation of mutations in mitochondria will reduce ATP production in a cell. There may be mutations or other changes that result in the insensitivity of membrane or nuclear receptors to endocrine hormones. Also the receptors may be altered by mutation or glucose cross-linking of membrane proteins.
3. Accumulation of wastes ("clinkers") in cells such as lipofuscins affect cell function. When I was a kid I used to shovel clinkers, brown chunks of glassy material, out of my grandmother's coal-burning furnace. Obviously, if the clinkers were not shoveled out, one could not get any more fuel in the furnace to burn. Something approaching that may occur due to the buildup of lipofuscins, yellowish-brown lipids or proteinaceous chemicals, that cells can't dispose of. Lysosomes become dysfunctional when they are filled with lipofuscins. Cells filled with clinkers become senescent and slow function; e.g., neuron conduction velocity slows with advancing age. These wastes are the by-products of the lysosomal and peroxisomal oxidation of certain fats by free radicals or peroxides. Clinker theory is also linked to the free radical and superoxide theory of aging. In 1968, a study was done of enzymatically-digested cadavers. It showed lipofuscin buildup directly proportional to the age of the cadaver.
4. Loss of telomeres
that cap the ends of chromosomes leads to the death of the cell. Cells
cannot
reproduce without these chromosomal caps. Pieces of telomeres are lost
very
gradually over many mitotic cell divisions. This may explain the
Hayflick
effect. But embryonic and, regrettably, cancer cells use an enzyme
called
telomerase that rebuilds telomeres! Cancer cells are immortal.
They are
also like embryonic cells in that they divide rapidly and migrate to
new locations.
Therefore, the discovery of telomerase and telomeres does not
necessarily lead
to human immortality. If abnormal cells marked for apoptosis acquired
telomeres, they would have a strong chance of becoming cancerous.
{{{Illustrate
processes.]]]
Critical Thinking
1. Criticize the term "bad cholesterol" for LDLs.
2. Explain the relationship between cigarette smoking and cancer in the lung and colon.
3. Who contributes more genes to a male offspring, mom or dad or are the contributions the same? Explain your answer.
4. Why is cancer more prevalent in older people? Similarly, why has cancer increased generally in all age groups over the 20th century?
Cyber Surfin'
See great graphic and photo images of cells in action at Cells Alive! - http://www.cellsalive.com/index.htm .
For more detail about organelles and their physiology from M.I.T., see the 7.01 Cell Biology Hypertext, http://www.mit.edu:8001/afs/athena/course/other/esgbio/www/cb/cbdir.html .
From Biology Multimedia in France, see cell animations that include actin and myosin ratcheting at http://www.biomultimedia.net/archiv/muscle.htm.
For an online learning program on mitosis and
meiosis, see
the Biology Project - Cell Biology from the University of
Arizona. Go to
http://www.biology.arizona.edu/cell_bio/cell_bio.html
. To see microtubules in mitotic spindles, from the University
of North
Carolina, see http://www.bio.unc.edu/faculty/goldstein/lab/movies.html.
The Howard Hughes Medical Institute's Bio-Interactive has a great site for cell biology, e.g., sex determination and the y chromosome at http://www.hhmi.org/biointeractive/
Review of
Important Concepts
Cells
I. The cell theory of Oken,
Schleiden and
Schwann stated that all living organisms are composed of cells.
II.
The Function of Cells
A.
The cell volume/area ratio decreases as cells get larger.
1.
This decreases the area available for transport of materials into and
out of
the cell.
III.
The Structure of Cells
A.
Prokaryotic cells do not have a nucleus or other membrane-bound
organelles.
B.
Eukaryotic cells have a membrane-bound nucleus and other membrane-bound
organelles.
IV.
Transport Between Fluid Compartment or from Air to a Fluid Compartment
A.
Fluid Compartments in the Human Body.
1.
The extracellular compartments include blood plasma and interstitial
fluid.
2.
The intracellular compartment resides inside cells.
A.
Transport Across Membranes
1.
The cell membrane is a fluid bilayer of proteins and phospholipids.
2.
Proteins of the cell membrane include receptors.
a. Membrane receptors can bind to peptide
hormones, lipoprotein carriers, neurotransmitters and viruses.
b. Membrane receptors may be parts of
channels for ions and molecules.
3.
Membrane proteins include channels and gated channels for ions and
specific
molecules.
4. Plasma
membrane proteins have polypeptide chain, glycolipid and
carbohydrate molecules that serve as cellular cement and cell
recognition
proteins that are important in immunity.
5. The
plasma membrane is semipermeable, basically screening molecules
according to their size.
B.
Types of Transport
1.
Passive transport occurs due to the kinetic energy of small particles.
a.
Diffusion is the process in which molecules move passively from a
high concentration area to a low concentration area.
b.
Oxygen, water, carbon dioxide and ammonia are common molecules that
move into and out of cells by diffusion.